Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Zonisamide is a broad-spectrum antiepilepsy drug approved in the United States for the adjunctive treatment of partial seizures in adults with epilepsy. Studies in Japan have established zonisamide as effective and safe for use in children, but there is limited information from the United States concerning its use in pediatric patients. This chart-review study was conducted to evaluate the efficacy, safety, and appropriate dosage of zonisamide for treating seizures in pediatric and adolescent patients. Charts of 50 pediatric patients (mean age 9.1 years, range 9 months to 20 years) who received zonisamide were evaluated for demographic characteristics, seizure types, dosage (mean = 15.8 mg/kg/day), response, concurrent medications, and adverse events. After treatment, 8 patients were seizure-free, and 11 others had > or =50% improvement in seizure control, including 11 of the 28 patients for whom treatment with six or more antiepileptic drugs was insufficient. Thirty-one patients experienced at least one adverse event while receiving zonisamide, and 14 discontinued as a result.
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PMID:Use of zonisamide in pediatric patients. 1587 18

Nefiracetam is a novel pyrrolidone-type nootropic agent, and it has been reported to possess a potential for antiepileptic therapy as well as cognition-enhancing effects. We investigated the anticonvulsant and neuroprotective effects of nefiracetam in kainic acid-induced seizures of rats, compared with levetiracetam and standard antiepileptic drugs. Subcutaneous injection of kainic acid (10 mg/kg) induced typical behavioral seizures such as wet dog shakes and limbic seizures and histopathological changes in the hippocampus (degeneration and loss of pyramidal cells in CA1 to CA4 areas). Nefiracetam (25, 50 and 100 mg/kg po) had no effect on the behavioral seizures and dose-dependently inhibited the hippocampal damage. In contrast, levetiracetam, a pyrrolidone-type antiepileptic drug, inhibited neither. Valproic acid and ethosuximide prevented the hippocampal damage without attenuating the behavioral seizures as nefiracetam. Zonisamide and phenytoin did not inhibit the behavioral seizures, while zonisamide enhanced the hippocampal damage and phenytoin increased the lethality rate. Carbamazepine inhibited the behavioral seizures at 50 mg/kg and enhanced that at 100 mg/kg, and it completely inhibited the hippocampal damage at both doses. We have previously reported that anticonvulsant spectrum of nefiracetam paralleled that of zonisamide, phenytoin or carbamazepine in standard screening models. However, the pharmacological profile of nefiracetam was closer to valproic acid or ethosuximide than that of zonisamide, phenytoin or carbamazepine in this study. These results suggest that anticonvulsant spectrum and mechanism of nefiracetam are distinct from those of standard antiepileptic drugs, and nefiracetam possesses a neuroprotective effect that is unrelated to seizure inhibition.
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PMID:Anticonvulsant and neuroprotective effects of the novel nootropic agent nefiracetam on kainic acid-induced seizures in rats. 1612 14

Zonisamide (Zonegran) has been used extensively worldwide (>2 million patient-years experience) for the effective treatment of a broad range of epilepsy indications. Four randomised, placebo-controlled trials (duration <or=6 months) in the United States and Europe (848 patients in total) have shown doses of zonisamide >or=300 mg/day to be efficacious in treating refractory partial seizures in adults. In a pivotal European study, zonisamide 500 mg/day was significantly superior to placebo in reducing the frequency of complex partial seizures (-51% versus -16%), all partial seizures and all seizures, with dose-dependent benefit provided over a 100-500 mg/day dose range. Supporting trials have confirmed significant increases in reduction in median seizure frequency (up to 41%) and responder rates (35-42%) compared with placebo following zonisamide 400-600 mg/day, enabling 20-27% of patients to attain >or=75% reduction in seizure frequency. Pooled data from all four placebo-controlled trials demonstrate an excellent tolerability and safety profile; adverse events are generally of mild-moderate severity with few leading to discontinuation, and incidence of serious adverse events is comparable to placebo. These data support the use of zonisamide in combination with commonly used antiepileptic drugs to provide efficacious and well-tolerated treatment for patients with refractory partial seizures.
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PMID:Zonisamide as adjunctive therapy for refractory partial seizures. 1631 44

Zonisamide (Zonegran), a novel antiepileptic drug (AED) approved in Europe for the adjunctive treatment of refractory partial seizures in adults, has undergone extensive evaluation in pre- and post-marketing double-blind and open-label studies in Japan (where zonisamide is used widely to treat partial and generalised seizures in adults and children). These data indicate that the clinical benefit of zonisamide extends across a range of seizure types and patient ages. In an analysis based on a mixture of controlled and open studies in adults and children with partial seizures, 51-57% responded to zonisamide treatment (achieving >or=50% reduction in baseline seizure frequency). Efficacy extends across a range of generalised seizures and 22-66% of adults and children experiencing tonic-clonic, tonic, clonic, myoclonic or absence seizures responded to treatment. Even greater responder rates have been reported when zonisamide was used as monotherapy for partial seizures and generalised seizures in patients refractory to other AEDs or with newly diagnosed epilepsy. Zonisamide is also efficacious in paediatric epilepsy syndromes, including Lennox-Gastaut Syndrome, West Syndrome and Ohtahara Syndrome. Across the spectrum of epilepsy syndromes studied, zonisamide is well-tolerated with a low incidence of adverse events, which are generally mild and CNS-related. These data indicate that zonisamide represents a valuable broad-spectrum option for the treatment of epilepsy.
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PMID:Zonisamide in the management of epilepsy--Japanese experience. 1632 7

Zonisamide is an antiepileptic drug used as adjunctive therapy for refractory partial seizures in adults. Because of the multiple mechanisms of action, it shows a broad spectrum of anticonvulsant activity and has been effective in several types of seizures, including partial and generalized seizures, tonic-clonic seizures and absence seizures in patients unresponsive to other anticonvulsants. Myoclonic epilepsy, Lennox-Gastaut syndrome and infantile spasms have also been treated effectively with zonisamide. Recent clinical studies have demonstrated additional potential for therapeutic use in neuropathic pain, bipolar disorder, migraine, obesity, eating disorders and Parkinson's disease. Despite adverse events, zonisamide is relatively safe and well tolerated in patients, and shows low discontinuation rate. It has a good pharmacokinetic profile and a low drug interaction potential. Zonisamide is considered as a drug that effectively reduces the frequency of partial seizures.
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PMID:Zonisamide: review of its use in epilepsy therapy. 1634 Dec 90

Long-term efficacy, tolerability and safety of antiepileptic drug (AED) therapy is essential given the chronic nature of epilepsy. Zonisamide (Zonegran), a novel AED with a broad range of mechanisms of action contributing to its antiseizure efficacy, has been evaluated extensively for the long-term management of epilepsy. Open-label extension studies in the United States and Europe suggest continued efficacy of zonisamide in long-term treatment without development of adverse events further to those seen in registration studies. Baseline seizure frequency is reduced by approximately 40-70% during long-term treatment for up to 2 years, and 30-50% of patients attain >or=50% reduction in seizure frequency across all categories of seizure and durations of treatment. Preliminary data indicate a progressive decline in seizure frequency with continued zonisamide treatment. Zonisamide is well tolerated in long-term use, with a trend towards decreasing incidence of generally mild adverse events over time and a low rate of withdrawal during chronic use. Nephrolithiasis and other serious adverse events are infrequent, and can be minimised by appropriate management and patient education. This profile of maintained efficacy, tolerability and safety during sustained administration in combination with other AEDs supports zonisamide as a valuable adjunctive agent in the long-term management of refractory partial epilepsy.
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PMID:Practical prescribing and long-term efficacy and safety of zonisamide. 1640 43

Zonisamide (Zonegran), a novel antiepileptic drug (AED) approved recently in Europe as adjunctive therapy for refractory partial seizures in adults, has been used extensively in Japan and the United States. A substantial body of clinical experience has accumulated over a 14-year period, allowing the properties and pharmacologic/clinical profiles of zonisamide to be clearly defined. Zonisamide is structurally distinct from other AEDs and has multiple and complementary mechanisms of action, which likely contribute to its efficacy across a broad range of epilepsy types. Zonisamide has a long T1/2 enabling once-daily dosing, linear pharmacokinetics and minimal interaction with other drugs; plasma levels of commonly administered AEDs and oral contraceptives are unaffected by concomitant zonisamide. Effective control of partial seizures (up to 51% decrease in seizure frequency) is attained at doses of >or=300 mg/day, and optimal titration and maintenance dosing schedules have been established. The adverse event profile is well defined; in common with most AEDs, most adverse events are central nervous system-related (e.g. somnolence, dizziness, tiredness). Adverse events may be minimised with appropriate patient management. Zonisamide therefore has many characteristics considered desirable in an AED and represents a valuable addition to the therapeutic options for treating epilepsy in Europe.
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PMID:Introduction to zonisamide. 1641 70

The long-term effects of zonisamide as monotherapy or adjunctive therapy were investigated in patients with seizure disorders. One hundred twelve adult neurology patients treated with zonisamide were retrospectively identified through a chart review; 90 patients (n=45 monotherapy, n=45 adjunctive therapy) who received zonisamide for 3 months were included in the efficacy-evaluable population, and all 112 patients were included in the safety population. The average duration of treatment was 24.3 months (range, 3-46 months), and the average zonisamide dosage was 324 mg/day (range, 100-1000 mg/day). Thirty-eight of 90 patients (42%; n=25 monotherapy, n=13 adjunctive therapy) were seizure-free, and an additional 26 patients (29%; n=9 monotherapy, n=17 adjunctive therapy) had 50% seizure frequency reduction at the last follow-up visit. Thirty of 112 patients (27%) reported mild to moderate adverse events, such as weight loss (5.4%), fatigue (4.5%), and sedation (2.7%). Zonisamide, as monotherapy or adjunctive therapy, was a safe, effective, and well-tolerated long-term treatment option in patients with various seizure types.
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PMID:Long-term efficacy and safety of monotherapy and adjunctive therapy with zonisamide. 1654 80

The aim of this study was to evaluate the efficacy and safety of zonisamide monotherapy in a cohort of children and adolescents with various types of epilepsy. Retrospective review of charts of our institution from 2001 through 2004 identified 69 children (19 males and 50 females, mean age 13.2 years) with epilepsy on zonisamide monotherapy. Seizure count and side effect profile were maintained during therapy. Sixty-one percent had idiopathic generalized epilepsy, 4% symptomatic generalized epilepsy, and 35% partial-onset epilepsy. Zonisamide was the first-line and second-line monotherapy for 32% and 68% of patients, respectively. The mean duration of follow-up on treatment was 22 months (range 3-48 months). The overall efficacy of zonisamide was 75.4% (> or = 50% seizure frequency reduction: good responders). Sixty-seven percent of good responders became seizure-free. Seventy-nine percent of patients with partial epilepsy and 71% with generalized epilepsy were good responders, of whom 79% and 63% were free of seizure, respectively. Eighteen (26%) patients developed side effects: weight loss (9), cognitive impairment (3), sleepiness (3), dizziness (2), and decreased appetite (1). In seven patients (10%), zonisamide had to be discontinued: four due to side effects and three because of poor seizure control. Zonisamide was demonstrated to be effective as monotherapy in children with epilepsy.
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PMID:Efficacy and safety of zonisamide monotherapy in a cohort of children with epilepsy. 1664 93

Despite the major advances in antiepileptic drug (AED) therapeutics, about one third of patients with epilepsy still do not have adequate seizure control with currently available AEDs when prescribed as monotherapy. Typically, in this setting polytherapy with two or more AEDs is used. Zonisamide (ZNS) is a new AED effective in the treatment of refractory epilepsy and since it is only prescribed in polytherapy regimens, its interactions with other AEDs is of particular importance. The aim of this study was to isobolographically determine interactions between ZNS and four conventional AEDs: carbamazepine (CBZ), phenytoin (PHT), phenobarbital (PB), and valproate (VPA), in the mouse maximal electroshock (MES)-induced seizure model. The total brain concentrations of conventional AEDs and ZNS were measured with immunofluorescence and high-pressure liquid chromatography (HPLC), respectively, in order to determine any pharmacokinetic contribution in any observed interactions. With isobolography, synergistic interactions were observed for the combination of ZNS plus VPA and ZNS plus PHT at the fixed-ratio of 1:1, while additivity was observed for their combinations at the remaining dose ratios of 1:3 and 3:1. In contrast, the interactions between ZNS and PB and between ZNS and CBZ, applied at the fixed-ratios of 1:3, 1:1 and 3:1 proved to be additive. None of these AED combinations were associated with motor and long-term memory impairment. Furthermore, whilst brain AED concentrations were unaffected by ZNS, PHT significantly increased and PB reduced brain ZNS concentrations. Thus, the resultant interactions between ZNS and PHT and between ZNZ and PB were consequent to both pharmacodynamic and pharmacokinetic components. Finally, one can conclude that because of the synergistic pharmacodynamic interaction between ZNS and VPA, this combination might be useful in clinical practice.
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PMID:Interactions between zonisamide and conventional antiepileptic drugs in the mouse maximal electroshock test model. 1687 88


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